Background Radiation-induced lung injury (RILI) is a major dose-limiting toxicity in thoracic radiotherapy, and accumulating evidence implicates radiation-induced cellular senescence in its pathogenesis. This study aimed to investigate whether combination therapy with dasatinib and quercetin (DQ) could mitigate RILI by reducing senescent cell burden. Methods A rat model of RILI was established using a single 30 Gy irradiation to the right lung. Pulmonary pathological changes, fibrosis, DNA damage, and cellular senescence were assessed by histology, immunofluorescence, senescence-associated β-galactosidase staining, Western blotting and immunohistochemistry. Transcriptomic profiling was performed to explore the underlying molecular mechanisms. Results Compared with irradiation alone, DQ treatment significantly alleviated radiation-induced inflammatory cell infiltration and collagen deposition, reduced γH2AX levels, decreased senescence-associated markers p53, p21, and p16, and suppressed multiple senescence-associated secretory phenotype (SASP) factors. Transcriptomic analysis indicated that DQ-mediated effects were closely associated with activation of apoptotic pathways and modulation of p53, MAPK, PI3K-Akt and mitophagy signaling cascades. Conclusion DQ attenuated RILI in rats, with effects consistent with the reduced radiation-induced senescent cells and suppression of senescence-associated inflammatory responses.
Liu et al. (Fri,) studied this question.